Dr. Nicolas G. Loebel, Ondine Biomedical

The Silent Role of Biofilms in Chronic Disease Forums Biofilm Community Expert Interviews Dr. Nicolas G. Loebel, Ondine Biomedical

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    • #3002 Score: 0
      Harrison
      Keymaster
        2 pts

        One of the newer innovations in the area of bacterial biofilm eradication is based on an older, proven technology called photodisinfection or photodynamic therapy. It has a remarkable ability to destroy pathogenic biofilms, leaving the commensal, friendly bacterial behind. This technology has been commercialized by Ondine Biomedical, a Vancouver-based company that has successfully moved the technology out of the lab. One of their products, the Periowave system, is now used by periodontists and other dental professionals throughout Canada. Patients all over the world have been successfully treated with this unique, light-activated biofilm treatment solution.

        I interviewed “Nick” in his research and development office in Bothell, Washington. Here are just a few interesting tidbits from our eighty-minute interview.
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        Around World War II, as we are aware, the first antibiotics became available and these antibiotics were uniquely powerful. They provided means to eliminate infections that had otherwise defeated any hope of success. Many people died from even minor infections, which became consequently infected further and gangrene developed and so forth. The age of the Penicillins ushered in an incredible expansion in human lifespan. But it also brought with it a fundamental problem of microbial resistance. So, bacteria have three thousand genes, give or take, only half of which are conscripted to meet present day requirements. The other half represents an enormous evolutionary storehouse of knowledge, as to how to defeat things that were available and were around as antimicrobials eons ago.

        As a result, when bacteria see these modern synthetic antimicrobials, such as the newer antibiotics, they are often killed, but those that are not killed have upregulated genes to defeat those antimicrobials. And so, resistance is a terrible problem with antibiotics. Our technology is essentially focused on elimination of the resistance aspect, so that you can use it again and again without fear of the technology losing potency. That’s really the fundamental aspect. How to create a rapid effective microbicide that doesn’t harm human tissue and at the same time does not generate resistance.

        In our world, we see the majority of infections as being biofilm based. Planktonic infections may be limited to transient bacteriemias and so forth. But when an infection on any hard surface, for example like an implant (a titanium implant in the hip or in the mouth), or even in tissue, certainly in bone develops, it’s developing in this biofilm form where bacteria are coexisting in a sessile film. A matrix of external polysaccharides form, essentially provide for a home in which the bacteria can survive the onslaught of bodily-based attack and external antimicrobial attack.

        And it’s those biofilms really that present in 70%, perhaps as much as 80%, of all infections. So when we talk infection, we really talk biofilm. Now whether the biofilm has a polymicrobial nature, multiplicity of bacteria, or even pathogens other than bacteria (fungal components, viral components) that’s a matter of debate, but we certainly like the photodynamic approach which is broad spectrum enough to cover the pathogens I have just listed.

        The acute phase would generally imply more planktonic forms where bacteria are multiplying rapidly – the so called log phase of growth and are not necessarily adherent on a surface and therefore sessile. We don’t have a definition for when the transfer occurs other than to say, bacteria stop being motile, or as motile, and they start producing these colonies which then sense the presence of the other bacterial components and, in fact, start to upregulate genes and downregulate genes which promote the growth of the bacterial biofilm itself and slow down development of some species while up regulating development of others. So the biofilm can grow in a relatively repeatable way and can harbor, in the end, hundreds and hundreds of different kinds of species, all of which coexist to some degree and are reliant on another to some degree for survival.

        That’s really an interesting question. And it’s at the cutting edge of how you design drugs to combat infections that are no longer treatable using conventional therapies. Bacteria interact with a host in ways that are extraordinarily complex. And we work with top researchers in this field, Dr. Rich Darveau, the University of Washington. Mike Wilson, Dr. Wilson has been involved in the generation of photodynamic technologies from day one; certainly one of the founders of our company. Other numerous researchers as well. And bacteria fundamentally talk to the host in ways that create conditions necessary for their survival. So they minimize attack by the host or they generate factors, dismuting factors that can blunt the attack by the host and, in addition, create their own factors. These are virulence factors, things such as protease, which are enzymes that chew up collagen to create little hiding places for themselves. That’s how tissue gets necrotic and the bacteria can burrow ever deeper. There are bacteria that are able to, to defeat or modify the exchange of information between cells; so that they can enter the spaces between cells and ultimately the cells themselves and exist within the cell. These are intracellular pathogens that make it even more difficult for antibiotics to eradicate. And, in particular the cytokine, or chemical messenger process, that is the end result of the immunomodulatory process in humans, can be altered by bacteria by expressing other chemicals to which the host responds.

        Now let’s make sure that it’s understood that bacteria are required for health. We evolved with bacteria. If you eliminate the ability of laboratory animals to develop from the fetal stage with bacteria coexistent, they form abnormalities in the gut and everywhere and other places. Those bacteria have co-evolved with the human and again are leveraged by the human for health. These are the so-called commensal or good bacteria that we are aware are very important in the science of probiotics. Often they are Lactobacilli responsible for aiding digestion in the gut and so forth. Absence of those bacteria can lead to a whole range of conditions, some of which are not well understood today.

        But, in particular it is when those bacteria get out of balance, if you will. We tend to use more technical terms that that. When the microflora shifts from a predominately gram positive to a gram negative cross section, we tend to see the development of more pathogenic infection. And that’s when some external help is often required.

        See a 10 minute distillation of our interview — HD clip here.
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      • #3003 Score: 0
        Harrison
        Keymaster
          2 pts

          We’ve provided a 10 minute excerpt of the 80 minute interview, see the HD clip here.

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